Objectives: To describe and characterize a group of private insurance members taking multiple medications over a one-year period. Methods: Persons were selected for this polypharmacy analysis if they had at least five unique maintenance prescriptions in their pharmacy claims records for the period of January-March 2005, based on a customized list of chronic medications. The full set of pharmacy and medical claims for these members were evaluated for a twelve month period, October 2004 to September 2005. Standard descriptive statistics were calculated to characterize the population. Logistic regression models were used to assess the association of pharmacy claims and “safety events” (i.e., emergency department visits (ED) and hospitalizations (H)). Results: The final analytic sample, having both pharmacy and medical coverage for the 12-months, consisted of N=14,890 members ≥ 19 years of age (66% female), from four U.S. states. There were over 93,000 unique pharmacy claims with a monthly average of 6.3 per member. Males (M) and females (F) had similar averages (M=6.2; F=6.3), yet males were more likely to have ED (12.1%M vs. 10.8%F, p=0.022) and H (8.3%M vs. 6.3%F, p<0.0001). Unadjusted logistic regressions estimated the effect of medication claims on ED and H as OR=1.14, p<0.0001 and OR=1.18, p<0.0001, respectively. This implies 14% and 18% higher odds of ED or H, respectively, for every unit increase in monthly medications. Adjusting for age and gender does not substantially affect these results. Conclusions: Evaluating serious medical events in sub-populations taking multiple prescription medications provides important information for health insurers trying to reduce ED and hospitalizations. In a privately insured polypharmacy sub-population, there was a strong association with these safety events and increased average monthly pharmacy claims. Private insurers may wish to establish managed care programs to evaluate and improve the overall safety of their members taking higher numbers of monthly medications.